The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain.

Objectives: Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.

Methods: Rats (n ​= ​8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery.

Shear stress-induced restoration of pulmonary microvascular endothelial barrier function following ischaemia reperfusion injury requires VEGFR2 signalling.

Normal shear stress produced by blood flow is sensed by the vascular endothelium and required for maintenance of the homeostatic functions of the endothelium in systemic conduit and resistance vessels. Many critical illnesses are characterised by periods of abnormally reduced or absent shear stress in the lung (e.g.

Fragment Discovery by X-ray Crystallographic Screening Targeting the CTP Binding Site of Pseudomonas aeruginosa IspD.

With antimicrobial resistance (AMR) reaching alarming levels, new anti-infectives with unpreceded mechanisms of action are urgently needed. The 2-C-methylerythritol-D-erythritol-4-phosphate (MEP) pathway represents an attractive source of drug targets due to its essential role in numerous pathogenic Gram-negative bacteria and Mycobacterium tuberculosis (Mt), whilst being absent in human cells. Here, we solved the first crystal structure of Pseudomonas aeruginosa (Pa) IspD, the third enzyme in the MEP pathway and present the discovery of a fragment-based compound class identified through crystallographic screening of PaIspD.

Explanations for higher-than-expected all-cause mortality from April 2021: A scoping review.

Objectives: Many countries have continued to experience a higher-than-expected number of deaths following the peaks in mortality observed in the first year of the Covid-19 pandemic. This review aims to identify the different explanations proposed for sustained higher-than-expected mortality beyond the first pandemic year.

Study Design: Scoping review.